Programmed death-1 ligands are expressed in the majority of advanced serous epithelial ovarian cancer

Introduction: Immunotherapeutic strategies have been developed and tested in ovarian carcinoma patients, but no single approach has proven clinical effective yet. These disappointing clinical results were explained by immune escape mechanisms such as the immune suppressive pathway of the programmed death-1 (PD-1) receptor, and its ligands PD-L1 and PD-L2. Objective: We determined the prognostic importance of immune inhibitory ligands PD-L1 and PD-L2, in a well-defined homogeneous subgroup of epithelial ovarian cancer (EOC). Methods: PD-L1/L2 expression was evaluated in primary advanced serous EOC tissue of 127 patients by immunohistochemistry using tissue microarrays (TMAs). PD-L1/L2 expression, was correlated with the number of tumor infiltrating lymphocytes (TIL) and TIL-subsets data, i.e. CD8+ cytotoxic- (CTL), FoxP3+ regulatory- (Tregs) and CD45R0+ memory T-lymphocytes. Results: PD-L1 and PD-L2 expression was observed in 65 (61.9%) and 77 (73.3%) of 127 tumor samples, respectively. Prognosis was not influenced by the expression of PD-L1 or PD-L2 in advanced serous EOC patients. Moreover, PD-L1 expression did not correlate with the number of one of the TIL subsets. PD-L2 expression correlated negatively with the number of memory T-cells [odds ratio (OR), 0.2; 95% confidence interval (95% CI), 0.1-0.5; P = 0.001] and positively with the number of CTL (OR, 3.2; 95% CI, 1.1-9.5, P = 0.037). Conclusion: Despite high expression rates of PD-L1/L2, PD-Ls have no prognostic impact in advanced serous EOC. Blockade of the PD-1/PD-Ls pathway may not provide a beneficial effect for immunotherapeutic treatment of advanced serous EOC